Comparison of clarithromycin-sensitive and clarithromycin-resistant Mycobacterium avium strains isolated from AIDS patients during therapy regimens including clarithromycin.

OBJECTIVES: Sixteen Mycobacterium avium strains were isolated from the blood of eight AIDS patients over a period of months. All the patients were on combination therapies including clarithromycin, and all had treatment failure and relapses of M.avium bacteremia. Paired clarithromycin-sensitive and resistant M.avium strains isolated at the beginning of treatment and at the first relapse of bacteremia were compared.

METHODS: The M.avium isolates were identified after hybridization with DNA probes specific for M.avium rRNA and typed epidemiologically with random amplified polymorphic DNA analyses using three arbitrary primers. The rate of intracellular cell entry or the tumour necrosis factor alpha induction by the M.avium isolates were studied in human monocytes and J774 cells.

RESULTS: When the M.avium isolates were hybridized with the rRNA probes, we obtained lower hybridization values with clarithromycin-resistant isolates than with clarithromycin-sensitive isolates. This appeared to be due to smaller amounts of rRNA available for hybridization than to mutation of the 23S rRNA sequences in clarithromycin-resistant strains. The RAPD analyses showed that the clarithromycin-resistant isolates were clonally related to the clarithromycin-sensitive strains in six of the eight patients. The other two patients had a RAPD profile, suggesting a re-infection and/or polyclonal infection. The M.avium isolates obtained on day 0 and after the emergence of resistance to clarithromycin did not differ in terms of their intracellular entry rate, or in terms of tumour necrosis factor alpha induction.

CONCLUSIONS: We infer that M.avium strains isolated during bacteraemic relapses on combination therapies including clarithromycin are epidemiologically related to the initial strain and do not show changes in the rate of intracellular cell entry and in terms of tumour necrosis factor alpha induction. Re-infections and/or polyclonal infections however, although less frequent, can also occur.